Uveal melanoma: epidemiology, etiology, and treatment of primary disease

Benjamin A Krantz, Nikita Dave, Kimberly M Komatsubara, Brian P Marr, Richard D Carvajal, Benjamin A Krantz, Nikita Dave, Kimberly M Komatsubara, Brian P Marr, Richard D Carvajal

Abstract

Uveal melanoma (UM) is the most common intraocular malignancy and arises from melanocytes in the iris, ciliary body, or choroid. Early diagnosis and local treatment is crucial, as survival correlates with primary tumor size. However, approximately 50% of patients will develop metastatic disease with 6-12 months' survival from metastatic diagnosis. Genomic analyses have led to the development of gene-expression profiles that effectively predict metastatic progression; unfortunately, no adjuvant therapy has been shown to prolong survival to date. New insights into the molecular biology of UM have found frequent activating mutations in genes encoding for the G-protein α-subunit, GNAQ and GNA11, and improved understanding of the downstream signaling pathways MAPK, PI3K/Akt, and Hippo have afforded an array of new targets for treatment of this disease. Studies are under way with rationally developed regimens targeting these pathways, and novel agents are under development. We review the diagnosis, management, and surveillance of primary UM and the adjuvant therapy trials under way.

Keywords: GNA11; GNAQ; MAP kinase; MEK; ocular melanoma; uveal melanoma.

Conflict of interest statement

Disclosure RDC serves a consultant and/or advisory board member for AstraZeneca, Aura Biosciences, Iconic Therapeutics, Janssen, Merck, Novartis, Rgenix, and Thomson Reuters. BPM serves as a consultant for Aura Biosciences. The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Signaling pathways in uveal melanoma. Abbreviations: PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; Gα, G-protein alpha subunit; GDP, guanosine diphosphate; GPCR, g-protein coupled receptor; GTP, guanosine triphosphate; P, phosphate; RTK, Receptor tyrosine kinase.

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